Breast cancer, the most common cancer that kills women, recurs in families moe frequently than expected by change. Recent findings by King et al (Science 208:406, 1980) suggest that in some families there is a single gene predisposing to breast cancer, the locus of which is linked to the locus of the genetic marker glutamatepyruvate transaminase (GPT). this project seeks to confirm these findings and identify other gene loci linked to cancer susceptibillity genes. Large kindreds with 3 or more cases of breast cancer will be studied by pedigree analysis for evidence of a single gene increasing susceptibility to breast cancer. Maximum likelihood methods will be used to compare several genetic and environmental models. These families will be studied for genetic linkage to markers representing 28 loci. Prometaphase preparations of peripheral blood chromosomes will be examined for evidence of a deletion such as has been found in retinoblastoma and the aniridia-Wilm's tumor syndrome, and also, as has been found in this laboratory, in multiple endocrine neoplasia syndrome type II. Breasts removed for treatment of cancer frequently have many separate foci of cancer. We will examine the electrophoretic types of glucose-6-phosphate dehydrogenase (G6PD) in multiple separate tumors in breasts removed for treatment of cancer in women who are heterozygous for electrophoretic variants of G6PD. The finding of different single forms of G6PD in tumors removed from the same breast would indicate that the tumors are clones that arose from different cells, and may lead to insight into carcinogenesis in the breast.